title: CA-S27: a novel Lewis a associated carbohydrate epitope is diagnostic and prognostic for cholangiocarcinoma.
abstract: Early and specific diagnosis is critical for treatment of cholangiocarcinoma (CCA). In this study, a carbohydrate antigen-S27 (CA-S27) monoclonal antibody (mAb) was established using pooled CCA tissue-extract as immunogen. The epitope recognized by CA-S27-mAb was a new Lewis-a (Le(a)) associated modification of MUC5AC mucin. A Soybean agglutinin/CA-S27-mAb sandwich ELISA to determine CA-S27 in serum was successfully developed. High level of CA-S27 was detected in serum of CCA patients and could differentiate CCA patients from those of gastro-intestinal cancers, hepatomas, benign hepatobiliary diseases and healthy subjects with high sensitivity (87.5%) and high negative predictive value (90.4%). The level of serum CA-S27 was dramatically reduced after tumor removal, indicating tumor origin of CA-S27. Patients with high serum CA-S27 had significantly shorter survivals than those with low serum CA-S27 regardless of serum MUC5AC levels. Fucosyltransferase-III (FUT3) was shown to be a regulator of CA-S27 expression. Suppression of CA-S27 expression with siRNA-FUT3 or neutralization with CA-S27 mAb significantly reduced growth, adhesion, invasion and migration potentials of CCA cells in vitro. In summary, we demonstrate that serum CA-S27, a novel carbohydrate antigen, has potential as diagnostic and prognostic markers for CCA patients. CA-S27 involves in promoting cell growth, adhesion, migration and invasion of CCA cells.
authors.affiliation: Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Atit
authors.initials: A
authors.lastname: Silsirivanit
authors.forename: Norie
authors.initials: N
authors.lastname: Araki
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.forename: Kulthida
authors.initials: K
authors.lastname: Vaeteewoottacharn
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Narimatsu
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Sawaki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D001650:Bile Duct Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000276:immunology; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000276:immunology*; D002448:Cell Adhesion / Q000502:physiology; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000276:immunology; D003937:Diagnosis, Differential; D004067:Digestive System Neoplasms / Q000175:diagnosis; D004847:Epithelial Cells / Q000737:chemistry / Q000276:immunology; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D005260:Female; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D007983:Lewis Blood Group Antigens; D008107:Liver Diseases / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D055271:Mucin 5AC / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009844:Oligosaccharides / Q000276:immunology*; D011237:Predictive Value of Tests; D034622:RNA Interference; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009363:Neoplasm Proteins; D009844:Oligosaccharides; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase